Gray Zone Research Articles

The effects of presidential breakdowns on foreign policy in Latin America

AbstractPresidents and their ideologies have long been thought to be important explanatory variables in Latin American foreign policy, but little is known about how presidential breakdowns, a common form of leader change, affect foreign policy. I use a qualitative structured comparison to analyze the effects of nine presidential ousters on their successors’ foreign policies. I focus on cases in which the legitimacy of the process is in a gray zone, when narrative disputes are more likely to emerge. The findings indicate that incumbents politicize foreign policy when they use it to attain public support but accommodate it to congressional interests when they need support of Congress; meanwhile, international peers respond to presidential breakdowns according to their strategic and ideological rather than normative concerns. Even though Latin America is dominated by weak states, domestic politics, especially during crises, play a major role in explaining their foreign policies. Considering the role played by presidents in foreign policymaking, understanding this kind of presidential succession is essential.

Comparison Between Changes in Systolic-Pressure Variation and Pulse-Pressure Variation After Passive Leg Raising to Predict Fluid Responsiveness in Postoperative Critically Ill Patients

ObjectiveThe authors aimed to evaluate the precision of changes in systolic pressure variation after passive leg raising (PLR) as a predictor of fluid responsiveness in postoperative critically ill patients and to compare the precision of changes in pulse pressure variation after PLR (ΔPPVPLR) with changes in systolic pressure variation after PLR (ΔSPVPLR). DesignA prospective observational study. SettingA surgical intensive care unit of a tertiary hospital. Participants74 postoperative critically ill patients with acute circulatory failure were enrolled. InterventionsFluid responsiveness was defined as an increase of 10% or more in stroke volume after PLR, dividing patients into two groups: responders and nonresponders. Measurement and Main ResultsHemodynamic data were recorded at baseline and after PLR, and the stroke volume was measured by transthoracic echocardiography. 38 patients were responders, and 36 were nonresponders. ΔPPVPLR predicted fluid responsiveness with the areas under the receiver operating characteristic curves (AUC) of 0.917, and the optimal cut-off values were 2.3% with the grey zone of 1.6% to 3.3% including 19 (25.7%) patients. ΔSPVPLR predicted fluid responsiveness with the AUC of 0.908, and the optimal cut-off values were 1.9% with the grey zone of 1.1% to 2.0% including 18 (24.3%) patients. No notable distinction was observed between the AUC for ΔPPVPLR and ΔSPVPLR (p = 0.805) in predicting fluid responsiveness. ConclusionsΔSPVPLR and ΔPPVPLR could accurately predict fluid responsiveness in postoperative critically ill patients. There was no difference in the ability to predict fluid responsiveness between ΔSPVPLR and ΔPPVPLR.

The National Security Debacle: Escalating the Bald Conversations on Rural Banditry in Northern Nigeria

Scholarly preoccupation with socio-political development in Nigeria appeared to have dwelt more on the fulfillment of great expectations and much less on the uncertainties of social change brought about by democratization in Africa. Thus, when Huntington reflected on the possibility of reversal following the onset of ‘Third wave’ in Africa, the emphasis on social conflict is very instructive in the democratization process of many states in Africa. Whereas some democracies have managed to consolidate or are still democratizing, a few others have relapsed into reverse wave or at best, are caught up in what Thomas Carothers described as “The gray zone”. In Nigeria for example, after almost half a century of democratization, there is rising wave of atavistic consciousness or what Engels described as the “Lowest instinct or passion in man”, where the political space is characterized by rampaging non-state actors. In specific terms, the new wave of dramatic reverses relates to terrorist attacks, ethnic violence, armed banditry, farmers-herders imbroglio, cattle rustling, kidnapping for ransom, and unknown gunmen. In the circumstance, marauders and brigands now reign supreme over what is described as ungoverned space, prompting a convergence of expert opinions that Nigeria is fast degenerating unto a failed state. Among the various descriptions of criminal enterprises in Nigeria, there is scholarly preoccupation with the nuances and pattern of armed banditry. This paper seeks to deepen this preoccupation by scoping the infamy of rural banditry in northern Nigeria. It argues that, beyond the much-touted ethno-religious sentiment and convoluted diversity, the worsening human condition occasioned by the increasing parlous governance situation in the country, are more persuasive in explaining the dramatic wave of criminal enterprises. The theoretical perspective of Cohen and Felson which treat crime as the consequence of the convergence of a motivated offender, a vulnerable target and the absence of capable guardian, comes close to a real-life connotation of rural banditry in northern Nigeria. The paper recommends among others, the urgent need to ups the quality of good governance in order to address the human condition, and that a collaboration among the leadership strata in the wider society must demonstrate sufficient commitment to compliment government efforts in a genuine governance project that seeks to emancipate Nigeria from her current sorry state.

INNV-13. PREDICTION OF MGMT METHYLATION FOR GLIOBLASTOMAS USING AI MODELS. A COST-EFFECTIVE FRAMEWORK FOR LOW AND MIDDLE-INCOME COUNTRIES

Abstract BACKGROUND MGMT methylation (MGMTmet) is prognostic and predictive for patients with glioblastoma (GBM). However, financial constraints limit access to molecular tests, especially in low and middle-income countries. Artificial intelligence (AI) tools have emerged as a potentially cost-effective solution for identifying MGMTmet. Therefore, we are investigating if an AI model could select those at higher risk to present positive results for molecular confirmation, thus making a better resource allocation. METHODS We have selected GBM patients from the public image bank, The Cancer Imaging Archive, and we included all patients with a molecular evaluation of MGMTmet. We defined our volume of interest based on the ESTRO-ACROP 2016 guideline for GBM radiotherapy contouring and then extracted the radiomic features. The collected features underwent structured analysis, and a prediction model for MGMTmet was developed. We used a Random Forest algorithm to identify the most relevant features. Subsequently, the dataset was divided into training and validation sets. RESULTS We examined 100 patients with histologically classified high-grade gliomas and wild-type IDH, Sixty-one were unmethylated, and 39 were methylated. In this cohort, over 39,000 features were extracted. To avoid noise and overfitting, the 13 most predictive features were selected. They belong to the following feature classes: demographic, first order, Gray Level Size Zone Matrix, and Gray Level Co-occurrence Matrix. The preliminary model achieved an accuracy of 80% for predicting MGMTmet. CONCLUSION our preliminary results show a promising role for AI models in screening patients for molecular testing. This initiative demonstrates the utilization of research to bridge the public health gap. By sharing experiences and fostering collaboration, physicians can work towards mitigating healthcare inequalities in low-middle-income countries. In our future perspectives, we plan to enhance the algorithm's efficacy by incorporating qualitative human-generated features and expanding our sample size.

Discovering pericoronary adipose tissue differences between normal and atherosclerotic coronary segments with radiomics analysis

Abstract Introduction Pericoronary adipose tissue (PCAT) extracted from coronary CT angiography (CCTA) is a novel marker for coronary inflammation. Establishing correlation between PCAT changes and the vascular lesion itself is essential for using PCAT to monitor clinical and subclinical disease status. Past studies focused on patient-level and vessel-level PCAT differences. However, lesion-level PCAT differences beyond mean attenuation values are not well understood. Purpose To investigate the differences between PCAT adjacent to atherosclerotic plaques and PCAT adjacent to normal coronary segments using radiomics analysis. Material and Methods This study enrolled 100 consecutive patients who underwent CCTA. A total of 446 plaques were successfully annotated in 89 patients. The PCAT of these 446 plaques and also their normal segment counterparts were extracted. Following prior literature, adipose tissue was defined as voxels with attenuation ranging -190 to -30 HU. PCAT was extracted within 3 mm distance from the vessel wall, along the middle 10 mm of each plaque. The PCAT of normal coronary artery segments were extracted both proximal and distal with distance D mm to the plaque with 10 mm length. We used 3 different distances to define the normal segments (D={10, 20, 30}). PyRadiomics was used to generate radiomics features and the random forest classifier from Scikit-Learn was used to distinguish PCAT extracted adjacent to atherosclerotic plaques and PCAT adjacent to normal coronary segments. To minimize bias due to vessel diameter or shape and focus on the texture of PCAT, we included only the First Order, GLCM, GLDM, GLRLM, GLSZM and NGTDM features (total 93 features) from PyRadiomics. We used 5-fold cross validation splitted at patient-level to develop the classifier. Result The radiomics model achieved acceptable discrimination for D=30 mm (mean AUROC = 0.70), borderline discrimination for D=20 mm (mean AUROC=0.68) and D=10 mm (mean AUROC = 0.60). These results suggest a trend toward greater differences between PCAT further away from the lesion compared with PCAT adjacent to the lesion. The feature "Gray Level Size Zone Matrix (GLSZM): Low Gray Level Zone Emphasis" had the highest importance in 4 out of 5 folds in our D = 30 mm experiment. The mean value of this feature is significantly different for the PCAT adjacent to the lesions compared to PCAT extracted from the normal segments (0.152 vs 0.166, p=0.001). Conclusion We investigated the difference between PCAT adjacent to atherosclerotic plaques and PCAT adjacent to normal coronary segments using radiomics analysis. We found greater discrimination when the normal segments were extracted further away from the lesion, suggesting PCAT changes due to atherosclerosis may exist beyond the length of the plaque. Moreover, "Gray Level Size Zone Matrix (GLSZM): Low Gray Level Zone Emphasis" could serve as a novel radiomic biomarker to correlate PCAT changes to atherosclerosis.

Submaximal in addition to peak stress echocardiogram differentiates pathological LV dilatation from physiological dilatation and could help facilitate early heart failure diagnosis

Abstract Background Left ventricular dimensions in athletes overlap with those observed in patients with dilated cardiomyopathy (DCM). Among athletes with concomitant baseline low left ventricular ejection fraction (LVEF), the differentiation between the two entities may be difficult. Purpose We compared the role of changes in left ventricular ejection fraction (LVEF) during submaximal and maximal stress exercise echocardiography to facilitate the differentiation between athlete’s heart and DCM individuals with asymptomatic exercising individuals with a dilated left ventricle (LV) and borderline/low LVEF (48-54%). Methods 47 highly active asymptomatic individuals with DCM and mildly impaired LVEF, 52 athletes with borderline/low LVEF (grey zone athletes) and 44 athletes with a normal EF (healthy athletes) underwent a stress echocardiography on a semi-recumbent bike with an incremental ramp protocol of 25watt/min.Echocardiographic images were obtained at rest, submaximal (80% of predicted heart rate) and maximal exercise. Maximal exercise was classified as a heart rate 90-100% of the calculated maximum heart rate for their age. Results Both grey zone and healthy athletes achieved a greater increase in peak LVEF compared with DCM individuals (20.4% and 20.2% vs 4.6% respectively). The mean increase in LVEF from submaximal exercise to maximal exercise in healthy athletes and grey zone athletes was 7.0% and 3.4% (p<0.001) respectively whereas individuals with DCM showed a mean reduction in LVEF of -4.3% during this period. 8 (17%) of DCM individuals were able to increase LVEF ≥10% from rest to peak exercise, however most (96%) revealed a drop in LVEF as effort progressed from submaximal to maximal exercise.97.7% of control athletes were able to augment an EF ≥10% from rest to maximum exercise and continued to show an increase in LVEF from submaximal to maximal exercise. Whereas 47 (90.4%) grey zone athletes also showed an increase in LVEF >10% from rest to peak exercise, the remaining 5 (9.6%) were unable to augment this response and revealed a drop in contractile reserve from submaximal to maximal exercise, suggesting the possibility of an underlying diagnosis of DCM. Conclusion Healthy athletes and grey zone athletes show a greater contractile reserve compared to DCM athletes during exercise.Over 90% athletes and 10% DCM patients reveal an increase in LVEF >10% from baseline to peak exercise.Comparison of changes in LVEF between submaximal and maximal exercise reveals that 96% DCM patients and 9.6% grey zone athletes show a drop in in LVEF during this period. Failure to augment LVEF between submaximal and maximal exercise may identify grey zone athletes with DCM.

Impact of intravascular ultrasound parameters on revascularization decision in grey zone fractional flow reserve: data from IRIS FFR registry

Abstract Background The optimal revascularization strategy for coronary stenosis with grey-zone fractional flow reserve (FFR) value (0.75-0.80) is still debated. This study investigated the prognostic impact of the lesion characteristics measured by intravascular ultrasound (IVUS) in grey-zone FFR. Methods A total of 734 native coronary stenoses with grey-zone FFR in 734 patients from the prospective multicenter IRIS-FFR registry were simultaneously evaluated by IVUS. The primary outcome was a composite of cardiac death, myocardial infarction and target vessel revascularization. Results Among the 734 patients, revascularization was deferred for 293 patients and performed for 441. During a median follow-up of 4.4 years, the primary outcome occurred in 31 (10.6%) patients in deferred group and 42 (9.5%) in performed group. With the best cut-off values of 2.62 mm2 (area under curve 0.64) and 75% (area under curve 0.63), respectively, the minimal lumen area (MLA) and plaque burden (PB) at the MLA site were significant predictors of the primary outcome in the deferred group, whereas they were not predictive in the performed group. Revascularization performed group showed lower incidence rate of the primary outcome than deferral group in 348 patients with smaller MLA (<2.62 mm2) and larger PB (>75%) (19.3% vs. 36.8%, hazard ratio 0.58, 95% confidence interval [CI] 0.34-0.91, P=0.017), whereas other patients showed similar incidence rate of primary outcome between two groups (15.7% vs. 19.8%, hazard ratio 0.78, 95% CI 0.47-1.31, P=0.35). Conclusions For coronary stenoses with grey-zone FFR and smaller MLA and larger PB measured by IVUS, revascularization was associated with better clinical outcomes than deferral. The incorporation of FFR and IVUS may improve the revascularization decision in native coronary stenoses with grey-zone FFR.

Reliability of pulse pressure and stroke volume variation in assessing fluid responsiveness in the operating room: a metanalysis and a metaregression

BackgroundPulse pressure and stroke volume variation (PPV and SVV) have been widely used in surgical patients as predictors of fluid challenge (FC) response. Several factors may affect the reliability of these indices in predicting fluid responsiveness, such as the position of the patient, the use of laparoscopy and the opening of the abdomen or the chest, combined FC characteristics, the tidal volume (Vt) and the type of anesthesia.MethodsSystematic review and metanalysis of PPV and SVV use in surgical adult patients. The QUADAS-2 scale was used to assess the risk of bias of included studies. We adopted a metanalysis pooling of aggregate data from 5 subgroups of studies with random effects models using the common-effect inverse variance model. The area under the curve (AUC) of pooled receiving operating characteristics (ROC) curves was reported. A metaregression was performed using FC type, volume, and rate as independent variables.ResultsWe selected 59 studies enrolling 2,947 patients, with a median of fluid responders of 55% (46–63). The pooled AUC for the PPV was 0.77 (0.73–0.80), with a mean threshold of 10.8 (10.6–11.0). The pooled AUC for the SVV was 0.76 (0.72–0.80), with a mean threshold of 12.1 (11.6–12.7); 19 studies (32.2%) reported the grey zone of PPV or SVV, with a median of 56% (40–62) and 57% (46–83) of patients included, respectively. In the different subgroups, the AUC and the best thresholds ranged from 0.69 and 0.81 and from 6.9 to 11.5% for the PPV, and from 0.73 to 0.79 and 9.9 to 10.8% for the SVV. A high Vt and the choice of colloids positively impacted on PPV performance, especially among patients with closed chest and abdomen, or in prone position.ConclusionThe overall performance of PPV and SVV in operating room in predicting fluid responsiveness is moderate, ranging close to an AUC of 0.80 only some subgroups of surgical patients. The grey zone of these dynamic indices is wide and should be carefully considered during the assessment of fluid responsiveness. A high Vt and the choice of colloids for the FC are factors potentially influencing PPV reliability.Trial Registration: PROSPERO (CRD42022379120), December 2022. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=379120

Abstract 18847: Apples to Apples: Cardiopulmonary Exercise Testing Findings in Healthy Athletes versus Equally Fit Patients With Hypertrophic Cardiomyopathy

Introduction: CPET is often used when athletes present for clinical evaluation of suspected pathology, including HCM. While lower than expected peak oxygen consumption (pVO 2 ) may raise suspicion for HCM, athletes with HCM frequently display normal or supranormal pVO 2 , limiting the diagnostic utility of this parameter. Hypothesis: We hypothesize that there will be differences in other CPET parameters between healthy athletes and equally fit individuals with established HCM. Aim: The aim of this study was to compare CPET parameters in healthy athletes and equally fit individuals with established HCM. Methods: Healthy athletes and HCM patients (percent predicted pVO 2 (ppVO 2 ) >90%, non-obstructive, no nodal agents) were identified who had cycle ergometer CPETs for research or clinical evaluation in a single lab. CPETs were compared between HCM patients and athletes matched (2:1 ratio) for age, sex, race, height, weight, and cardiorespiratory fitness (ppVO 2 ). Results: Consistent with matching, HCM (n=30, 43.6 ± 14.2 years) and athletes (n=60, 43.8 ± 14.9 years) groups had similar, supranormal pVO 2 (40.4 ± 9.0 vs. 41.2 ± 8.9 mL/kg/min, 125% vs. 124% predicted, n.s.). While many CPET parameters were similar between groups, HCM patients had worse ventilatory efficiency with lower end-tidal CO 2 at the ventilatory threshold (VT) (42.9 ± 6.4 vs. 45.7 ± 4.8, p= 0.02), higher early VE/VCO 2 slope (through VT, 25.4 ± 4.7 vs. 23.4 ± 3.1, p=0.02), and higher nadir of VE/VCO 2 (27.3 ± 4 vs. 25.2 ± 2.6, p<0.001). When stratified by ppVO 2 , these differences remained significant for those with ppVO 2 < and ≥100%. Using the recommended cut-off of <30, HCM patients were more likely to have abnormally high VE/VCO 2 nadir than athletes (20% vs. 5%, p= 0.03). Conclusion: Amongst equally fit individuals, ventilatory efficiency was worse in patients with HCM than in healthy athletes. Our results suggest ventilatory efficiency may be useful to integrate in with other diagnostic testing in “gray zone” clinical cases in which the diagnosis of HCM is being debated in athletes with LVH. Given ventilatory efficiency has been increasingly recognized as a key prognostic CPET parameter, future work should establish the prognostic value of VE/VCO 2 in HCM patients with intact cardiorespiratory fitness.

Practical application of the CA-62 tumor marker in the initial diagnosis of oncological disease of epithelial origin: assistance to the doctor in interpreting the results

Aim. Demonstration the possibility of practical application of the highly sensitive tumor marker CA-62 in the initial diagnosis in asymptomatic patients with suspected cancer and/or the presence of pathological changes in instrumental studies, as well as describe the criteria for interpreting the results to help the doctor make a decision.
 Materials and methods. The article used the results and conclusions of blind clinical trials conducted to detect early stages of breast cancer (BC), prostate cancer (PC), colorectal cancer (CRC) and non-small cell lung cancer using the CA-62 tumor marker and other tumor markers. Statistical analysis was performed using the MedCalc program (MedCalc Software Ltd, Belgium). Diagnostic efficiency was assessed in terms of sensitivity, specificity, test accuracy, PPV and NPV, ROC analysis. The significance level was taken as p0.001.
 Results. The use of the standard cut-off value of 5000 U/ml of the CA-62 tumor marker makes it possible to achieve 97% sensitivity with 95% specificity in stage I BC. The combination of tumor markers CA-62 and CA 15-3 allows achieving 100% specificity in differentiation of BC and benign breast hyperplasia. The use of the CA-62 marker (6500 U/ml) in the gray zone of PSA 2.510 ng/ml improves the accuracy of detecting PC in biopsy from 35 to 93.1% with 90% sensitivity and 97% specificity. The use of a combination of tumor markers (CA-625000 U/ml, CYFRA 21-12.5 ng/ml and CEA5 ng/ml) will allow the doctor to improve the efficiency of differentiating lung cancer from chronic obstructive pulmonary disease. The combined use of markers (CEA3.5 ng/ml) and (CA-625000 U/ml) achieves 100% specificity with 97% sensitivity in detecting early stages of CRC.
 Conclusion. The article shows the possibilities of using the CA-62 marker, as well as new algorithms for the detection and differentiation of early stages of BC, PC, non-small cell lung cancer and CRC and benign neoplasms using the CA-62 marker in primary diagnosis. The use of the CA-62 tumor marker or its combination with other diagnostic methods can be a useful strategy for a comprehensive assessment of the risk of malignant neoplasms and increasing the diagnostic sensitivity of detecting early stages of cancer.

HBcrAg-based risk score performs better than the HBV DNA-based scores for HCC prediction in grey zone patients who are HBeAg-negative

Background & AimsRisk scores have been designed to predict the development of hepatocellular carcinoma (HCC) in treatment-naive patients with chronic hepatitis B (CHB). However, little is known about their predictive accuracy in HBeAg-negative patients in the grey zone (GZ). We aimed to develop a HBcrAg-based HCC risk score and explore whether it outperforms other risk scores in GZ patients. MethodsTwo retrospective cohorts of HBeAg-negative patients with American Association for the Study of Liver Diseases-defined GZ were established for derivation and validation (Taiwanese, N = 911; Japanese, N = 806). All of them were non-cirrhotic at baseline and remained treatment-naive during the follow-up. The primary endpoint was HCC development. ResultsIn a median follow-up period of 15.5 years, 85 patients developed HCC in the derivation cohort. We found that age, sex, alanine aminotransferase, platelet count, and HBcrAg, but not HBV DNA levels, were independent predictors and a 20-point GZ-HCC score was developed accordingly. The 10-year and 15-year area under the ROC curve (AUROC) ranged from 0.83 to 0.86, which outperformed the HBV DNA-based HCC risk scores, including REACH-B and GAG-HCC scores (AUROC ranging from 0.66 to 0.74). The better performance was also validated in EASL- and Asian Pacific Association for the Study of the Liver-defined GZ patients. These findings remained consistent in the validation cohort. Finally, the low-risk and high-risk GZ patients (stratified by a score of 8) had an HCC risk close to inactive CHB and immune-active CHB patients, respectively, in both cohorts. ConclusionsThe HBcrAg-based GZ-HCC score predicts HCC better than other HBV DNA-based risk scores in GZ patients who are HBeAg-negative patients, which may help optimise their clinical management. Impact and implicationsWe have developed a risk score based on HBcrAg, which has shown better predictive ability for HCC compared with other risk scores based on HBV DNA. Using a score of 8, GZ patients can be classified into low- and high-risk groups, which can guide follow up and early treatment, respectively. This validated risk score is a valuable tool for optimising the management of GZ patients who are HBeAg-negative.

Violence and the Gray Zone of Politics: An Outline for a Relational Approach

In this essay, I illustrate a relational perspective on gray zone politics, one that shifts the substantive and analytic focus of inquiry from groups and places (this trafficking gang, those neofascists, etc.) to the hidden links between them and established actors within the political field (be they state authorities, elected officials, or members of security forces).

“I no longer agree with Hitler to exterminate them…”. Teaching The Holocaust to Malaysian BA German-Students Through Selected History Films

The article describes experiences in teaching the sensitive topic of the industrial extermination of European Jews during World War II (the Holocaust) in the BA German programme at Universiti Putra Malaysia. The topic was covered in a history course and supported by the use of international feature films. Based on a summary of Malaysia-Israel relations, the relevance of the topic in the teaching of German as a foreign language is highlighted, and the teaching objectives, pedagogical approach and results of a film project are presented. The article aims to answer the questions of how Malaysian students perceived history films on the Holocaust and whether it was possible to achieve a more differentiated view of the Holocaust, at least among some students. As part of a comprehensive history film project on the Second World War, three history films dealing with the persecution and extermination of European Jews were screened and analysed in class. The film 'The Grey Zone' (USA, 2001) was selected for this article and students' responses and attitudes to challenging questions, provided as qualitative data, are discussed. Three historical literacies – Content Knowledge, Historical Empathy/Perspective Recognition and Narrative Analysis (Metzger 2007) – provided the theoretical framework for the history film project.

Exploring the Ethical Gray Zone of Adopting New Surgical Techniques: The Case of Retzius-Sparing Radical Prostatectomy.

Developing, practicing, and implementing novel surgical techniques is imperative for all surgical specialties, but the differences between minor variations, major variations requiring specific informed consent, and human experimentation can sometimes be difficult for surgeons and institutional review boards (IRB) to establish. Retzius-sparing prostatectomy is a technical modification of conventional prostatectomy, involving substantial changes in surgical steps and anatomic landmarks, with reported improvements in some early outcomes at the cost of a significant learning curve and some uncertainty in long-term oncologic outcomes. Here, we present a review of the ethical considerations of developing new surgical techniques and how they should apply to Retzius-sparing prostatectomy. The need for special informed consent when a surgeon begins to adopt this approach and the need for IRB revision when collecting outcomes for publication.

Impact of the 3rd Edition of the Bethesda System for Reporting Thyroid Cytopathology on Grey Zone Categories

Introduction: Thyroid Bethesda Reporting System is a six-tiered system that aims to bring uniformity in reporting thyroid cytology and improve the communication with clinicians. The system has achieved its goal as a presurgical diagnostic method; however, it remains a screening method in the grey zone categories, namely atypia of undetermined significance (AUS) and follicular neoplasm (FN). The book recently released the 3rd edition, following the recent changes in thyroid pathology. One of the most important novelties is subgrouping AUS category and FN to be able to make a better risk stratification in these categories. Our group aims to retrospectively analyze a large dataset based on the new TBSRTC, with a focus on the grey zone categories. Methods: Only patients who underwent lobectomy or total thyroidectomy were included, allowing for direct comparison between cytological and histopathological results. Cytological evaluations, based on the TBSRTC 3rd edition, were methodically compared with their respective histopathological results, enabling a comprehensive analysis. Results: Of the 244 patients (female:male ratio = 8.8:1, mean age = 56), a total of 252 nodules were evaluated. A distinction was noted with 79 nodules (31%) diagnosed as AUS and 173 nodules (69%) as FN. Intriguingly, the risk of malignancy (ROM) for AUS-overall stood at 44.3%, with AUS-nuclear atypia at 50% and AUS-other at 43.2%. Although the AUS subdivisions did not demonstrate statistical significance, a significant disparity was observed in their distribution, with 15% as AUS-nuclear atypia compared to 85% as AUS-other. This disparity raises the question: Could AUS-other be considered the new waste-basket category in the TBSRTC 3rd edition? Using the TBSRTC 3rd edition as a base, we added a subclassification for FN nodules based on the presence or absence of papillary thyroid carcinoma (PTC) nuclear features. Our findings showed that differentiating FN with oncocytic characteristics correlated well with histological outcomes and ROMs. Though retrospective in design with inherent bias potential, our data suggest a possible improvement in PTC case segregation in the FN category when differentiating between FN nodules with and without PTC nuclear features. Conclusion: Our retrospective study sheds light on the potential advantages of the TBSRTC 3rd edition, particularly in refining the AUS and FN categories for thyroid nodules. The clear disparity in AUS subcategories raises important questions about their classification and potential future refinements. Moreover, the differentiation of FN nodules based on PTC nuclear features holds a promising approach for better risk stratification.

Immunoglobulin light chain transcript detection by ultrasensitive RNA in situ hybridization for B-cell lymphoma diagnosis.

Evaluation of B-cell clonality can be challenging in the interpretation of lymphoid infiltrates on tissue sections. Clonality testing based on IG gene rearrangements analysis by PCR (IG-PCR) is the gold standard. Alternatively, B-cell clonality can be assessed by the recognition of immunoglobulin light chain (IgLC) restriction, by immunohistochemistry (IHC), chromogenic in situ hybridization (ISH) or flow cytometry (FC). IG-PCR requires molecular facilities, and FC requires cell suspensions, both not widely available in routine pathology units. This study evaluates the performance of B-cell clonality detection by IgLC-RNAscope® (RNAsc) in a group of 216 formalin-fixed, paraffin-embedded samples including 185 non-Hodgkin B-cell lymphomas, 11 Hodgkin lymphomas (HL) and 20 reactive samples. IgLC-RNAsc, performed in parallel with FC in 53 cases, demonstrated better performances (93% vs 83%), particularly in diffuse large B-cell lymphoma (98% vs 71%) and follicular lymphoma (93% vs 83%) diagnosis. IgLC-RNAsc was also superior to IHC and ISH especially in samples with limited tumor cell content, where IG-PCR was not informative. Performed for the first time on mediastinal lymphomas, IgLC-RNAsc identified monotypic IgLC transcripts in 69% of primary mediastinal large B-cell lymphoma (PMBCL) and 67% of mediastinal gray zone lymphomas (MGZL). IGK/L double-negative cells were detected in 1 PMBCL, 2 MGZL, and all classical HL, while monotypic IgLC expression appeared to be a hallmark in nodular lymphocyte-predominant HL. IgLC-RNAsc demonstrates to be a powerful tool in B-cell lymphoma diagnosis, above all in challenging cases with limited tumor cell content, ensuring in situ investigations on mechanisms of Ig regulation across lymphoma entities.

Interfacial Polymerization Produced Magnetic Particles with Nano-Filopodia for Highly Accurate Liquid Biopsy in the PSA Gray Zone.

Magnetic particles are leading separation materials for biological purification and detection. Existing magnetic particles, which almost rely on molecule-level interactions, however, often encounter bottlenecks in highly efficient cell-level separation due to the underestimate of surface structure effects. Here, immune cell-inspired magnetic particles with nano-filopodia (NFMPs) produced by interfacial polymerization for highly efficient capture of circulating tumor cells (CTCs) and further accurate clinical diagnosis of prostate cancer are reported . The unprecedented construction of nano-filopodia on polymer-based magnetic particles is achieved by introducing electrostatic interactions in emulsion interfacial polymerization. Due to the unique nano-filopodia, the NFMPs allow remarkably enhanced CTCs capture efficiency (86.5%±2.8%) compared with smooth magnetic particles (SMPs, 35.7%±5.7%). Under the assistance of machine learning by combining with prostate-specific antigen (PSA) and free to total PSA (F/T-PSA), the NFMPs strategy demonstrates high sensitivity (100%), high specificity (93.3%), and a high area under the curve (AUC) value (98.1%) for clinical diagnosis of prostate cancer in the PSA gray zone. The NFMPs are anticipated as an efficient platform for CTCs-based liquid biopsy toward early cancer diagnosis and prognosis evaluation.

Proposing new seismic texture attributes based on novel gray level matrix with application to salt dome detection

The exploration of new hydrocarbon resources requires a detailed image of the subsurface geological structures. Interpreting seismic sections is one of the most common ways of accurately imaging the Earth's subsurface. Automated seismic section interpretation requires accurate delineation of the target geobody through seismic section segmentation. Texture analysis of images is one of the common tools for seismic section segmentation for target geobody identification. Exploration of geological phenomena e.g. the salt dome, buried channels, etc., is very important in the field of hydrocarbon exploration and production due to the possibility of creating stratigraphic and structural hydrocarbon traps, creating potential for subsurface energy storage and drilling hazards. They have textural differences with their surrounding environment, and therefore the analysis of seismic sections using textural attributes to determine the geometry of these events is one of the challenges facing interpreters. Gray level co-occurrence matrix (GLCM) is the commonly used tool for textural analysis of seismic images, based on which several attributes have been introduced. Optimal adjustment of numerous input parameters in GLCM attributes and their strong dependence on the dip of events are the drawbacks of this method. In this paper, we proposed new seismic attributes based on the newly introduced gray level matrices (GLM) consisting of gray level run length matrix (GLRLM), gray level size zone matrix (GLSZM), gray level difference matrix (GLDM), and normalized gray level dependence matrix (NGLDM). The new proposed seismic attributes depend on fewer input parameters for adjustment than conventional attributes while increasing accuracy in event detection, and even GLSZM-based attributes are independent of the phenomena dip. The efficiency of the proposed attributes was evaluated on the real field and synthetic seismic data containing a salt dome and its results were compared with conventional GLCM-based attributes. The qualitative and quantitative results showed that in addition to the methodological superiority of the newly introduced gray level matrices compared to the GLCM, the accuracy of the proposed attributes was also increased in the salt dome detection. Moreover, it seems that the linear transform to grayscale performed better than the non-linear one in distinguishing the salt dome from the surrounding sediments. But the main challenge is distinguishing the salt dome texture from the weak layering which the nonlinear transform has done better than the linear one.

Passive leg raising test induced changes in plethysmographic variability index to assess fluid responsiveness in critically ill mechanically ventilated patients with acute circulatory failure

BackgroundPassive leg raising (PLR) reliably predicts fluid responsiveness but requires a real-time cardiac index (CI) measurement or the presence of an invasive arterial line to achieve this effect. The plethysmographic variability index (PVI), an automatic measurement of the respiratory variation of the perfusion index, is non-invasive and continuously displayed on the pulse oximeter device. We tested whether PLR-induced changes in PVI (ΔPVIPLR) could accurately predict fluid responsiveness in mechanically ventilated patients with acute circulatory failure. MethodsThis was a secondary analysis of an observational prospective study. We included 29 mechanically ventilated patients with acute circulatory failure in this study. We measured PVI (Radical-7 device; Masimo Corp., Irvine, CA) and CI (Echocardiography) before and during a PLR test and before and after volume expansion of 500 mL of crystalloid solution. A volume expansion-induced increase in CI of >15% defined fluid responsiveness. To investigate whether ΔPVIPLR can predict fluid responsiveness, we determined areas under the receiver operating characteristic curves (AUROCs) and gray zones for ΔPVIPLR. ResultsOf the 29 patients, 27 (93.1%) received norepinephrine. The median tidal volume was 7.0 [IQR: 6.6–7.6] mL/kg ideal body weight. Nineteen patients (65.5%) were classified as fluid responders (increase in CI > 15% after volume expansion). Relative ΔPVIPLR accurately predicted fluid responsiveness with an AUROC of 0.89 (95%CI: 0.72–0.98, p < 0.001). A decrease in PVI ≤ −24.1% induced by PLR detected fluid responsiveness with a sensitivity of 95% (95%CI: 74–100%) and a specificity of 80% (95%CI: 44–97%). Gray zone was acceptable, including 13.8% of patients. The correlations between the relative ΔPVIPLR and changes in CI induced by PLR and by volume expansion were significant (r = −0.58, p < 0.001, and r = −0.65, p < 0.001; respectively). ConclusionsIn sedated and mechanically ventilated ICU patients with acute circulatory failure, PLR-induced changes in PVI accurately predict fluid responsiveness with an acceptable gray zone. Trial registrationClinicalTrials.govNCT03225378.

Serum HBV RNA levels among untreated adults with chronic hepatitis B in distinct immune phases and liver histopathology statuses.

HBV RNA is a novel serum biomarker that reflects intrahepatic HBV covalently closed circular DNA (cccDNA) transcription activity. Serum HBV RNA levels among treatment-naïve adults during the natural history of chronic hepatitis B (CHB) and distinct liver histopathology statuses remain elusive. In our study, we include a total of 411 treatment-naïve CHB patients, among which 43 patients were HBeAg-positive immune-tolerant [IT(e+)], 84 patients were HBeAg-positive immune active [IA(e+)], 65 patients in HBeAg-negative immune active phases [IA(e-)], 149 patients were HBeAg-negative inactive phases [IC(e-)], and 70 patients were in Gray Zone (GZ). HBV RNA was measured in this cohort and its potential correlation with traditional serological markers and liver histopathology were analyzed. Our data showed that HBV RNA was strongly correlated with HBV DNA, HBeAg, HBsAg and ALT. Further subgroup analysis revealed a close correlation between HBV RNA and HBV DNA in patients in the IA (e+) and IA (e-) phases, but neither in IT(e+) nor IC(e-) phase. HBV RNA levels were consistently increased with the advanced degrees of hepatic inflammation, but not hepatic fibrosis. Of note, HBV RNA from HBeAg-positive patients negatively correlated with liver fibrosis, whereas HBV RNA from HBeAg-negative patients was weakly associated with liver inflammation. To sum up, serum HBV RNA shows a distinct profile among CHB patients in different immune statuses and hepatic histopathology stages/grades. Simultaneous testing of HBV RNA and traditional indicators might provide a comprehensive clinical assessment of CHB patients.